Cargando…

The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b

Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 b...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Yue-Zhi, Hsu, Hsing-Yu, Yang, Cheng-Wei, Lin, Yi-Ling, Chang, Sui-Yuan, Yang, Ruey-Bing, Liang, Jian-Jong, Chao, Tai-Ling, Liao, Chun-Che, Kao, Han-Chieh, Chang, Jang-Yang, Sytwu, Huey-Kang, Chen, Chiung-Tong, Lee, Shiow-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325102/
https://www.ncbi.nlm.nih.gov/pubmed/35890406
http://dx.doi.org/10.3390/pharmaceutics14071511
_version_ 1784756964164632576
author Lee, Yue-Zhi
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
author_facet Lee, Yue-Zhi
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
author_sort Lee, Yue-Zhi
collection PubMed
description Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm.
format Online
Article
Text
id pubmed-9325102
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93251022022-07-27 The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b Lee, Yue-Zhi Hsu, Hsing-Yu Yang, Cheng-Wei Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju Pharmaceutics Article Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm. MDPI 2022-07-21 /pmc/articles/PMC9325102/ /pubmed/35890406 http://dx.doi.org/10.3390/pharmaceutics14071511 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Yue-Zhi
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title_full The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title_fullStr The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title_full_unstemmed The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title_short The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
title_sort synergistic inhibition of coronavirus replication and induced cytokine production by ciclesonide and the tylophorine-based compound dbq33b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325102/
https://www.ncbi.nlm.nih.gov/pubmed/35890406
http://dx.doi.org/10.3390/pharmaceutics14071511
work_keys_str_mv AT leeyuezhi thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT hsuhsingyu thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT yangchengwei thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT linyiling thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT changsuiyuan thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT yangrueybing thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT liangjianjong thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT chaotailing thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT liaochunche thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT kaohanchieh thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT changjangyang thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT sytwuhueykang thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT chenchiungtong thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT leeshiowju thesynergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT leeyuezhi synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT hsuhsingyu synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT yangchengwei synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT linyiling synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT changsuiyuan synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT yangrueybing synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT liangjianjong synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT chaotailing synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT liaochunche synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT kaohanchieh synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT changjangyang synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT sytwuhueykang synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT chenchiungtong synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b
AT leeshiowju synergisticinhibitionofcoronavirusreplicationandinducedcytokineproductionbyciclesonideandthetylophorinebasedcompounddbq33b